1. Title: Stereotactic Ablative Radiotherapy (SABR) can be Safe and Effective for Treatment of Central and Ultra-Central Lung Tumors. Author: Aadel Chaudhuri, MD PhD Abstract #: 2014-A-2428-ASTRO Session title: Lung 1 - Novel Prognostic Factors and SBRT Date/Time: 2014-09-14 13:15 Location: Room D-1 Monitor number: 7

2.  Phase 2 trial performed by Timmerman et al. showed that stereotactic ablative radiotherapy with a dose fractionation of 60 Gy in 3 fractions was effective at controlling stage 1 T1-T2a N0M0 NSCLC (localized tumor ≤ 5 cm in diameter) with 95% local tumor control at 2y, and 32.6 months median overall survival.  Unfortunately, patients with centrally located tumors, defined as tumor location within 2cm of the proximal bronchial tree, experienced higher rates of severe toxicity (2y freedom from severe toxicity 54% for central tumor patients compared to 83% for peripheral tumor patients).  4 of 22 (18%) central lung tumor patients experienced grade 5 toxicity, where the safety monitoring board believed that SABR caused severe toxicity contributing to death.  Given these safety concerns, the followup RTOG 0236 phase 3 trial made tumor centrality one of its exclusion criteria. Indiana University Phase 2 Trial Timmerman et al, J of Clinical Oncology, 2006

3.  Four retrospective studies have since followed, showing that central lung tumor patients treated with SABR experience good local tumor control and acceptable levels of toxicity (Chang et al, IJROBP, 2008; Haasbeek et al, J of Thoracic Oncology, 2011; Bral et al, IJROBP, 2011; Rowe et al, J of Thoracic Oncology, 2012).  However, none of these studies used the RTOG 0816 definition of tumor centrality, and all included examples of patients with severe toxicity, with three including patients whose death appeared treatment-related (Haasbeek et al, J of Thoracic Oncology, 2011; Bral et al, IJROBP, 2011; Rowe et al, J of Thoracic Oncology, 2012).  The NEJM also published a report of fatal hemorrhage due to central airway necrosis, deemed to be from SABR to a central tumor adjacent to the right proximal bronchial tree (Corradetti et al, NEJM, 2012). Retrospective Studies on Central Lung Tumor SABR/SBRT

4. RTOG 0813 and Our Institutional Study  With the possibility that lung SBRT might be safe and effective for central NSCLC patients, RTOG 0813 was setup to study this issue prospectively.  RTOG 0813 Eligibility: Patients with T1-2 N0 M0 NSCLC, tumor size ≤ 5 cm, who are not candidates for complete surgical resection.  Centrality was defined as tumors within 2 cm of the proximal bronchial tree, or directly adjacent to the mediastinal or pericardial pleura.  Starting dose: 50 Gy in 5 fractions. Protocol allowed dose escalation up to 60 Gy in 5 fractions, if patients were seen to not have dose-limiting toxicity at lower doses.  We used the RTOG 0813 tumor centrality criteria, and compared its dosimetric constraints to patients treated in our institution.  We compared Peripheral and Central lung tumor patients treated with 50 Gy in 4-5 fractions. Toxicity levels were low for both groups, including for a subset of “ultra-central” tumor patients with tumors directly abutting the proximal bronchial tree.

5. Take Home Points  Central and Peripheral stage I-II NSCLC patients treated with SABR had similar outcomes, with local control at 2 years > 80%, and OS at 2 yrs of 70%.  Toxicity rates were low in both central and peripheral lung tumor patients, with no grade 5 toxicities and only one case of grade 4 toxicity, indicating that SABR is a safe modality for treatment of both groups.  Seven Ultra-Central tumor patients with tumors directly abutting the proximal bronchial tree, experienced no significant toxicities.  Ultra-Central tumor patients also had comparable rates of local control and survival as their less central counterparts.  Dosimetric analysis revealed that the RTOG 0813 central airway dosimetric constraints were most commonly infracted in our study, indicating they may be more conservative than necessary.  In summary, SABR appears to be a safe and effective modality for treatment of both central and peripheral lung tumors, including “ultra-central” tumors directly abutting the proximal bronchial tree.